Cited by 296Viral-associated cancers and disordersIgG4-Related and Inflammatory DiseasesLymphadenopathy Diagnosis and Analysis

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Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV ‐8‐negative multicentric Castleman disease

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Iwaki, Noriko, Fajgenbaum, David C., Nabel, Christopher S., Gion, Yuka, Kondo, Eisei, Kawano, Mitsuhiro, Masunari, Taro, Yoshida, Isao, Moro, Hiroshi, Nikkuni, Koji, Takai, Kazue, Matsue, Kosei, Kurosawa, Mitsutoshi, Hagihara, Masao, Saito, Akio, Okamoto, Masataka, Yokota, Kenji, Hiraiwa, Shinichiro, Nakamura, Naoya, Nakao, Shinji, Yoshino, Tadashi, Sato, Yasuharu·2016·American Journal of Hematology

DOI 10.1002/ajh.24242

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Abstract

Multicentric Castleman disease (MCD) describes a heterogeneous group of disorders involving systemic inflammation, characteristic lymph node histopathology, and multi‐organ dysfunction because of pathologic hypercytokinemia. Whereas Human Herpes Virus‐8 (HHV‐8) drives the hypercytokinemia in a cohort of immunocompromised patients, the etiology of HHV‐8‐negative MCD is idiopathic (iMCD). Recently, a limited series of iMCD cases in Japan sharing a constellation of clinical features, including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O) has been described as TAFRO syndrome. Herein, we report clinicopathological findings on 25 patients (14 males and 11 females; 23 Japanese‐born and two US‐born), the largest TAFRO syndrome case series, including the first report of cases from the USA. The median age of onset was 50 years old (range: 23–72). The frequency of each feature was as follows: thrombocytopenia (21/25), anasarca (24/25), fever (21/25), organomegaly (25/25), and reticulin fibrosis (13/16). These patients frequently demonstrated abdominal pain, elevated serum alkaline phosphatase levels, and acute kidney failure. Surprisingly, none of the cases demonstrated marked hypergammoglobulinemia, which is frequently reported in iMCD. Lymph node biopsies revealed atrophic germinal centers with enlarged nuclei of endothelial cells and proliferation of endothelial venules in interfollicular zone. 23 of 25 cases were treated initially with corticosteroids; 12 patients responded poorly and required further therapy. Three patients died during the observation period (median: 9 months) because of disease progression or infections. TAFRO syndrome is a unique subtype of iMCD that demonstrates characteristic clinicopathological findings. Further study to clarify prognosis, pathophysiology, and appropriate treatment is needed. Am. J. Hematol. 91:220–226, 2016. © 2015 Wiley Periodicals, Inc.

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Authors: Iwaki, N., Fajgenbaum, D. C., Nabel, C. S., Gion, Y., Kondo, E., Kawano, M., Masunari, T., Yoshida, I., Moro, H., Nikkuni, K., Takai, K., Matsue, K., Kurosawa, M., Hagihara, M., Saito, A., Okamoto, M., Yokota, K., Hiraiwa, S., Nakamura, N., Nakao, S., Yoshino, T., & Sato, Y.
Affiliations: Kanazawa University (JP)
University of Pennsylvania (US)
Okayama University (JP)
Kanazawa University Hospital (JP)
Chugoku Central Hospital (JP)
Shikoku Cancer Center (JP)
Niigata University (JP)
Niigata City General Hospital (JP)
Kameda Medical Center (JP)
Sapporo National Hospital (JP)
Eiju General Hospital (JP)
National Hospital Organization (JP)
Fujita Health University (JP)
Tokai University (JP)
Corresponding author: Sato, Yasuharu
ORCID: Fajgenbaum, David C.
Nabel, Christopher S.
Gion, Yuka
Kondo, Eisei
Kawano, Mitsuhiro
Masunari, Taro
Yoshida, Isao
Moro, Hiroshi
Matsue, Kosei
Hagihara, Masao
Yokota, Kenji
Hiraiwa, Shinichiro
Nakamura, Naoya
Nakao, Shinji
Sato, Yasuharu
Venue: American Journal of Hematology
Publisher: Wiley
Published: 2016-01-22
Volume: 91
Issue: 2
Pages: 220-226
ISSN: 0361-8609 (ISSN-L)
1096-8652
DOI: 10.1002/ajh.24242
OpenAlex: W2179940598
Cited by: 296
References: 39
Citations by year: 2026: 28 · 2025: 30 · 2024: 30 · 2023: 19 · 2022: 31 · 2021: 29 · 2020: 34 · 2019: 23 · 2018: 34 · 2017: 30 · 2016: 7
FWCI: 10.48
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: American Journal of Hematology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
Health Sciences › Medicine › Rheumatology › IgG4-Related and Inflammatory Diseases
Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphadenopathy Diagnosis and Analysis
Keywords: TAFRO syndrome, multicentric Castleman disease, idiopathic multicentric Castleman disease, thrombocytopenia, anasarca, fever, reticulin fibrosis, organomegaly, cytokine storm, lymph node histopathology, endothelial cell proliferation, corticosteroid therapy, acute kidney injury, hypergammaglobulinemia
MeSH terms: Adult, Aged, Female, Castleman Disease, Humans, Lymph Nodes, Male, Middle Aged, Plasma Cells, Platelet Count, Syndrome, Thrombocytopenia, Herpesvirus 8, Human, Young Adult

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Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV ‐8‐negative multicentric Castleman disease

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